Breast cancer-related mortality may be reduced with oophorectomy in select patients with early-stage BRCA1-related disease

medwireNews: Survival results support the use of oophorectomy for breast cancer patients with stage I or II Oestrogen receptor-negative disease who test positive for the BRCA1 mutation.

“These results extend the rationale for testing all women with early-stage breast cancer for BRCA1 Mutations at the time of diagnosis”, say Steven Narod, from Women’s College Research Institute in Toronto, Ontario, Canada, and co-workers.

The adjusted hazard ratio (HR) for breast cancer-related deaths after an average of 12.5 years of follow-up was a significant 0.38 for the 219 BRCA1 carriers who had their ovaries removed versus the 192 who did not.

The HR was 0.57 for the 121 women with BRCA2 mutations who underwent oophorectomy versus the 133 who did not but, as this did not reach significance, the researchers say further research is required “to confirm the benefit of oophorectomy in this population.”

The HR for breast cancer-related mortality was significant for women with oestrogen receptor-negative tumours irrespective of BRCA1/2 status who underwent oophorectomy versus those who did not, at 0.07, with a trend for those with oestrogen receptor-positive disease, at 0.76.

Further analysis indicated that the breast cancer-related survival benefit was highest in women who had their ovaries removed within 2 years of diagnosis, lasted for around 15 years and included women who underwent oophorectomy after the age of 50 years, the researchers add in JAMA Oncology.

The impact of oophorectomy in older women indicates that the ovaries may continue to produce androgen after the menopause, affecting cancer risk and progression directly or through aromatisation to oestrogen, suggest Steven Narod et al.

“If the latter is true, then we would expect maximum risk reduction to be achieved through the administration of an aromatase inhibitor after oophorectomy”, they observe.

The authors caution that the results do not apply to women with advanced disease and note the study was performed before the introduction of aromatase inhibitor therapy or Epidermal growth factor receptor genetic testing.

Nevertheless, they conclude: “These data, coupled with emerging data on the unique sensitivities of BRCA-related breast cancers to certain classes of chemotherapy, and the mortality benefit derived from chemotherapy, and from contralateral mastectomy, suggest that women with newly diagnosed breast cancer and a BRCA mutation might benefit from treatments that are tailored to the hereditary subgroup.”